Direct oral anticoagulant- vs vitamin K antagonist-related nontraumatic intracerebral hemorrhage

Georgios Tsivgoulis; Vasileios-Arsenios Lioutas; Panayiotis Varelas; Aristeidis H Katsanos; Nitin Goyal; Robert Mikulik; Kristian Barlinn; Christos Krogias; Vijay K Sharma; Konstantinos Vadikolias; Efthymios Dardiotis; Theodore Karapanayiotides; Alexandra Pappa; Christina Zompola; Sokratis Triantafyllou; Odysseas Kargiotis; Michael Ioakeimidis; Sotirios Giannopoulos; Ali Kerro; Argyrios Tsantes; Chandan Mehta; Mathew Jones; Christoph Schroeder; Casey Norton; Anastasios Bonakis; Jason Chang; Anne W Alexandrov; Panayiotis Mitsias; Andrei V Alexandrov

doi:10.1212/WNL.0000000000004362

Direct oral anticoagulant- vs vitamin K antagonist-related nontraumatic intracerebral hemorrhage

Neurology. 2017 Sep 12;89(11):1142-1151. doi: 10.1212/WNL.0000000000004362. Epub 2017 Aug 16.

Authors

Georgios Tsivgoulis¹, Vasileios-Arsenios Lioutas², Panayiotis Varelas², Aristeidis H Katsanos², Nitin Goyal², Robert Mikulik², Kristian Barlinn², Christos Krogias², Vijay K Sharma², Konstantinos Vadikolias², Efthymios Dardiotis², Theodore Karapanayiotides², Alexandra Pappa², Christina Zompola², Sokratis Triantafyllou², Odysseas Kargiotis², Michael Ioakeimidis², Sotirios Giannopoulos², Ali Kerro², Argyrios Tsantes², Chandan Mehta², Mathew Jones², Christoph Schroeder², Casey Norton², Anastasios Bonakis², Jason Chang², Anne W Alexandrov², Panayiotis Mitsias², Andrei V Alexandrov²

Affiliations

¹ From the Department of Neurology (G.T., N.G., A.K., J.C., A.W.A., A.V.A.), University of Tennessee Health Science Center, Memphis; Second Department of Neurology (G.T., A.H.K., C.Z., S.T., M.I., A.B.), "Attikon" Hospital, School of Medicine, National and Kapodistrian University of Athens, Greece; Department of Neurology (V.-A.L., C.N.), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA; Department of Neurology (P.V., C.M., M.J., P.M.), Henry Ford Hospital, Detroit, MI; Department of Neurology (A.H.K., S.G.), University of Ioannina School of Medicine, Greece; International Clinical Research Center (R.M.), Neurology Department, St. Anne's Hospital and Masaryk University, Brno, Czech Republic; Department of Neurology (K.B.), Dresden University Stroke Center; Department of Neurology (C.K., C.S.), St. Josef-Hospital, Ruhr University of Bochum, Germany; Division of Neurology (V.K.S.), Yong Loo Lin School of Medicine, National University of Singapore; Department of Neurology (K.V.), Democritus University of Thrace, Alexandroupolis, Greece; Department of Neurology (E.D., A.P.), University of Thessaly, Larissa; Second Department of Neurology (T.K.), AHEPA University Hospital, Aristotelian University of Thessaloniki; Acute Stroke Unit (O.K.), Metropolitan Hospital, Piraeus; Laboratory of Haematology and Blood Bank Unit (A.T.), "Attikon" Hospital, School of Medicine, National and Kapodistrian University of Athens, Greece; Australian Catholic University (A.W.A.), School of Nursing, Sydney, Australia; and Department of Neurology (P.M.), University of Crete, Heraklion, Greece. tsivgoulisgiorg@yahoo.gr.
² From the Department of Neurology (G.T., N.G., A.K., J.C., A.W.A., A.V.A.), University of Tennessee Health Science Center, Memphis; Second Department of Neurology (G.T., A.H.K., C.Z., S.T., M.I., A.B.), "Attikon" Hospital, School of Medicine, National and Kapodistrian University of Athens, Greece; Department of Neurology (V.-A.L., C.N.), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA; Department of Neurology (P.V., C.M., M.J., P.M.), Henry Ford Hospital, Detroit, MI; Department of Neurology (A.H.K., S.G.), University of Ioannina School of Medicine, Greece; International Clinical Research Center (R.M.), Neurology Department, St. Anne's Hospital and Masaryk University, Brno, Czech Republic; Department of Neurology (K.B.), Dresden University Stroke Center; Department of Neurology (C.K., C.S.), St. Josef-Hospital, Ruhr University of Bochum, Germany; Division of Neurology (V.K.S.), Yong Loo Lin School of Medicine, National University of Singapore; Department of Neurology (K.V.), Democritus University of Thrace, Alexandroupolis, Greece; Department of Neurology (E.D., A.P.), University of Thessaly, Larissa; Second Department of Neurology (T.K.), AHEPA University Hospital, Aristotelian University of Thessaloniki; Acute Stroke Unit (O.K.), Metropolitan Hospital, Piraeus; Laboratory of Haematology and Blood Bank Unit (A.T.), "Attikon" Hospital, School of Medicine, National and Kapodistrian University of Athens, Greece; Australian Catholic University (A.W.A.), School of Nursing, Sydney, Australia; and Department of Neurology (P.M.), University of Crete, Heraklion, Greece.

PMID: 28814457
DOI: 10.1212/WNL.0000000000004362

Abstract

Objective: To compare the neuroimaging profile and clinical outcomes among patients with intracerebral hemorrhage (ICH) related to use of vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs) for nonvalvular atrial fibrillation (NVAF).

Methods: We evaluated consecutive patients with NVAF with nontraumatic, anticoagulant-related ICH admitted at 13 tertiary stroke care centers over a 12-month period. We also performed a systematic review and meta-analysis of eligible observational studies reporting baseline characteristics and outcomes among patients with VKA- or DOAC-related ICH.

Results: We prospectively evaluated 161 patients with anticoagulation-related ICH (mean age 75.6 ± 9.8 years, 57.8% men, median admission NIH Stroke Scale [NIHSS_adm] score 13 points, interquartile range 6-21). DOAC-related (n = 47) and VKA-related (n = 114) ICH did not differ in demographics, vascular risk factors, HAS-BLED and CHA₂DS₂-VASc scores, and antiplatelet pretreatment except for a higher prevalence of chronic kidney disease in VKA-related ICH. Patients with DOAC-related ICH had lower median NIHSS_adm scores (8 [3-14] vs 15 [7-25] points, p = 0.003), median baseline hematoma volume (12.8 [4-40] vs 24.3 [11-58.8] cm³, p = 0.007), and median ICH score (1 [0-2] vs 2 [1-3] points, p = 0.049). Severe ICH (>2 points) was less prevalent in DOAC-related ICH (17.0% vs 36.8%, p = 0.013). In multivariable analyses, DOAC-related ICH was independently associated with lower baseline hematoma volume (p = 0.006), lower NIHSS_adm scores (p = 0.022), and lower likelihood of severe ICH (odds ratio [OR] 0.34, 95% confidence interval [CI] 0.13-0.87, p = 0.025). In meta-analysis of eligible studies, DOAC-related ICH was associated with lower baseline hematoma volumes on admission CT (standardized mean difference = -0.57, 95% CI -1.02 to -0.12, p = 0.010) and lower in-hospital mortality rates (OR = 0.44, 95% CI 0.21-0.91, p = 0.030).

Conclusions: DOAC-related ICH is associated with smaller baseline hematoma volume and lesser neurologic deficit at hospital admission compared to VKA-related ICH.

Publication types

Comparative Study
Meta-Analysis
Multicenter Study
Review
Systematic Review

MeSH terms

Administration, Oral
Aged
Anticoagulants / administration & dosage*
Atrial Fibrillation / complications
Atrial Fibrillation / diagnostic imaging
Atrial Fibrillation / drug therapy
Brain / diagnostic imaging
Brain / drug effects
Cerebral Hemorrhage / complications
Cerebral Hemorrhage / diagnostic imaging
Cerebral Hemorrhage / drug therapy*
Cross-Sectional Studies
Female
Humans
Male
Observational Studies as Topic
Prospective Studies
Stroke / complications
Stroke / diagnostic imaging
Stroke / drug therapy*
Treatment Outcome
Vitamin K / antagonists & inhibitors*

Substances

Anticoagulants
Vitamin K